Is LAMB3 p.Ser97= (c.291A>C) pathogenic?

LAMB3 p.Ser97= (c.291A>C) is classified Benign in LAMB3 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 67.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with amelogenesis imperfecta type 1A.

What condition is associated with LAMB3 p.Ser97= (c.291A>C)?

LAMB3 p.Ser97= (c.291A>C) is associated with amelogenesis imperfecta type 1A, junctional epidermolysis bullosa, non-Herlitz type, junctional epidermolysis bullosa Herlitz type (ClinVar).

LAMB3 p.Ser97=

Q: How common is LAMB3 p.Ser97= (c.291A>C) in the general population?

LAMB3 p.Ser97= (c.291A>C) is common (popmax 67.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.291A>C · rs2076356 · VCV255592

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 67.6%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

amelogenesis imperfecta type 1A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.59	GERP -3.5, phastCons 0.05
Overall
CADD	4.308	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 67.6% Middle Eastern · 4,076/6,030 alleles

Filtering AF 65.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 65.2%

Overall 61.3% 982,045/1,601,282 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	75.2%	1
Finnishnot grpmax-eligible	70.8%	1
Ashkenazi Jewishnot grpmax-eligible	68%	1
Middle Easterngrpmax	67.6%	1
European (non-Finnish)	64.9%	2
Remaining individualsnot grpmax-eligible	59.4%	2
South Asian	49.8%	2
Admixed American	46.2%	2
African / African-American	41.6%	2
East Asian	28.9%	3

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: LAMB3
Protein: p.Ser97=
Coding: c.291A>C
MANE Select: NM_000228
dbSNP: rs2076356
Type: single nucleotide variant
Location: chr1:209638541 (GRCh38)
Gene constraint: LOEUF 0.829 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.55
Residue 97: the laminin n-terminal domain

Full LAMB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

amelogenesis imperfecta type 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: junctional epidermolysis bullosa, non-Herlitz type junctional epidermolysis bullosa Herlitz type junctional epidermolysis bullosa

Similar variants

LAMB3 c.1132+5G>A Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.1133-22G>A Pathogenic ★★ same condition
LAMB3 c.1288+1G>T Pathogenic/Likely pathogenic ★★ same condition
LAMB3 c.1486-1G>A Likely pathogenic ★★ same condition
LAMB3 c.1597+1G>T Likely pathogenic ★★ same condition
LAMB3 c.2701+2T>C Likely pathogenic ★★ same condition
LAMB3 c.28+1G>T Likely pathogenic ★★ same condition
LAMB3 c.3228+1G>A Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/lamb3-p-ser97 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown